Β-enamino Carbonyl Compounds Research Articles

Photooxidative C-C double bond cleavage of β-enaminocarbonyl compounds: toward selective N-formylation of amines.

A photooxidative C-C double bond cleavage of electron-deficient β-enaminocarbonyl compounds possessing a silyl group at the α-position to the nitrogen atom using methylene blue (MB) as the photosensitizer was explored. Photochemically generated 1O2 was added across the CC bond with the aid of a tethered silyl group to cleave it and form N-formylamines. This reaction protocol exhibited compatibility with numerous β-enaminocarbonyl substrates, including those with various N-alkyl, N-benzyl and N-aryl substituents.

A versatile core–shell hetero-nanostructure catalysed chemo-selective synthesis of β-enamino carbonyl compounds

A core–shell hetero-nanostructure has been developed and used for the enamination of β-carbonyl compounds.

Heterocyclizations of β-alkoxy, β-diaminoalkyl, and related β-functionalized enones (enals) with NCN-binucleophiles

This review provides a detailed survey of the present literature data on β-alkoxyvinyl- and β-enaminocarbonyl compounds as CCC bis-electrophiles in reactions with the common NCN-binucleophiles. The focus is put mostly on the reactions leading to low-molecular-weight and functionalized pyrimidines as the products that are of special interest as building blocks for drug discovery

Recent Advances in Synthesis and Reactions of β-Amino-α ,β -Enones (Enaminones).

β-Amino-α,β-enones or β-enamino carbonyl compounds are versatile synthons intermediates for the construction of various bio-active heterocyclic compounds and have been established as multipurpose synthetic precursors in organic syntheses and in pharmaceutical developments. In this work, we will discuss the different synthetic routes to obtain β-amino-α,β-enones or β-enamino carbonyl compounds, their reactions, and their utility in the construction of organic frameworks and heterocyclic ring systems. Structurally, β- amino-α,β-enones are attractive intermediates that syndicate the ambident behaviours of nucleophilicity and electrophilicity of enones at the same time. β-amino-α,β-enones have been known as acceptors in both 1,2- and 1,4- additions that make them good intermediate compounds for annulation to different heterocycles.

Chemistry and spectroscopy of cross-conjugated and pseudo-cross-conjugated quinolinium-ethynyl-benzoate mesomeric betaines

Abstract The three isomers 1-methylquinolinium-2-, 3-, and 4-ethynyl(phenyl-4-carboxylates) belong to two distinct types of heterocyclic mesomeric betaines. The quinolinium substituted in position 3 is a cross-conjugated mesomeric betaine (CCMB), whereas the quinolinium derivatives substituted in positions 2 and 4 are members of the class of pseudo-cross-conjugated mesomeric betaines (PCCMBs). While the charges are strictly separated within the common π-electron system of the CCMB according to the canonical formulae, the charges are effectively but not exclusively delocalized in the PCCMBs because cumulenoid resonance forms including electron sextet structures without external octet stabilization can be formed in accordance with the definition of PCCMBs. As a consequence, despite being closely related structures, the three isomers differ in their chemical and spectroscopic behaviors. Thus, on trying to hydrolyze the ester group of the methyl quinolinium-2-ethynyl-benzoate into the corresponding acid by subsequent treatment with sodium hydroxide in methanol and aqueous hydrochloric acid at pH 3, the acetal methyl 1,1-dimethoxy-2-(quinolinium-ylidene)ethyl]benzoate and the corresponding β-enamino carbonyl compound were formed, respectively. The corresponding acids of the 2- and 4-substituted quinolinium-ethynyl-benzoates were obtained by a modified procedure. On deprotonation, the resulting cross-conjugated quinolinium-3-ethynyl-benzoate betaine proved to be stable, whereas the corresponding pseudo-cross-conjugated quinolinium-2- and -4-ethynyl-benzoate betaines decomposed. Frontier orbital profiles were calculated, and IR and Raman spectra of the starting materials were measured and calculated to analyze the differences of CCMBs and PCCMBs of mesomeric betaines possessing triple bonds. A higher contribution of the cumulenoid resonance forms to the overall structure of the PCCMBs was determined.

Chemoselective Reduction of α-Cyano Carbonyl Compounds: Application to the Preparation of Heterocycles

β-Aminoacrylates are reactive intermediates that are useful building blocks in synthesis. General methods for their preparation typically afford α and β disubstitution patterns or β only. Molecules with only α-substituents (β-hydrogen) are much less well-known. A chemoselective reductive tautomerization of α-cyanoacetates, using DIBAL-H, has been developed to access these valuable synthons. α,β-Unsaturated cyanoacetates and α-cyanoketones can, also, be selectively reduced via this methodology. A series of heterocycles were prepared using these β-enamino carbonyl compounds.

Synthesis of functionalized 2,3-dihydropyrroles by oxidative radical cyclization of N-Sulfonyl β-enamino esters with alkenes

Oxidative radical cyclization of N-sulfonyl β-enamino esters with alkenes has been developed. Substituted 2,3-dihydropyrroles were produced when the reactions were carried out in the presence of CAN and Cu(OAc)2 as the oxidant. Intramolecular cyclization of β-enamino carbonyl compounds having an alkenyl and an alkynyl side chain proceeded to afford the corresponding bicyclic products, respectively.

ChemInform Abstract: Synthesis of Functionalized 2‐Vinyl‐2,3‐dihydropyrroles and 3‐Methylene‐1,2,3,4‐tetrahydropyridines by Palladium‐Catalyzed Cyclization of β‐Enaminocarbonyl Compounds with Allylic Bisacetates.

A palladium-catalyzed cyclization of β-enaminocarbonyl compounds with allylic bisacetates is described. 2-Vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines were produced from the reaction of β-enaminocarbonyl compounds with 1,4-diacetoxy-2-butene and 2-methylene-1,3-propanediol diacetate, respectively.

Synthesis of functionalized 2-vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines by palladium-catalyzed cyclization of β-enaminocarbonyl compounds with allylic bisacetates

A palladium-catalyzed cyclization of β-enaminocarbonyl compounds with allylic bisacetates is described. 2-Vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines were produced from the reaction of β-enaminocarbonyl compounds with 1,4-diacetoxy-2-butene and 2-methylene-1,3-propanediol diacetate, respectively.

ChemInform Abstract: Unusual Reaction of Thiomalonamide with 5,5‐Dimethyl‐2‐phenylaminomethylidene‐1,3‐cyclohexanedione.

β-Enaminocarbonyl compounds are commonly used in heterocyclic synthesis as convenient and readily available 1,3-dielectrophile 3C synthones [1, 2]. In previous work [3], we showed that the reaction of 5,5-dimethyl-2-phenylaminomethylidenecyclohexane-1,3-dione (1) with cyanothioacetamide gives the quinoline derivative 2. We established that the reaction of thiomalonamide 3 with dimedone derivative 1 yields 6-thioxopyrimidine-5-carboxamide 4 instead of the expected 3-carbamoyl analog of quinoline 2. Alkylation of carboxamide 4 with benzyl chloride gives benzyl derivative 5. The structures of carboxamides 4 and 5 were supported by IR, H-NMR, and C-NMR spectroscopy, HPLC/MS, elemental analysis, and the results of a H-C HMBC NMR experiment for carboxamide 4 (Fig. 1). The H NMR spectrum of carboxamide 4 shows signals for two amide groups and one methylene group, as well as singlets for protons H-4 and NH. The HPLC/MS shows a peak [M+H] with m/z 213.6. Atom H-4 in the pyrimidine ring in the H-C HMBC spectrum gives four correlation peaks: δ-8.78/127.1 (H-4/C-5), 8.78/159.6 (H-4/C-2), 8.78/163.7 (H-4/5-CONH2), and 8.78/179.7 ppm (H-4/C-6). The CH2 group protons give two cross peaks: δ-3.69/159.6 (CH2/C-2) and 3.69/167.8 ppm (CH2/CO). The finding of cross peaks at δ 7.17/41.1

Unusual reaction of thiomalonamide with 5,5-dimethyl-2-phenylaminomethylidene-1,3-cyclohexanedione

β-Enaminocarbonyl compounds are commonly used in heterocyclic synthesis as convenient and readily available 1,3-dielectrophile 3C synthones [1, 2]. In previous work [3], we showed that the reaction of 5,5-dimethyl-2-phenylaminomethylidenecyclohexane-1,3-dione (1) with cyanothioacetamide gives the quinoline derivative 2. We established that the reaction of thiomalonamide 3 with dimedone derivative 1 yields 6-thioxopyrimidine-5-carboxamide 4 instead of the expected 3-carbamoyl analog of quinoline 2. Alkylation of carboxamide 4 with benzyl chloride gives benzyl derivative 5. The structures of carboxamides 4 and 5 were supported by IR, H-NMR, and C-NMR spectroscopy, HPLC/MS, elemental analysis, and the results of a H-C HMBC NMR experiment for carboxamide 4 (Fig. 1). The H NMR spectrum of carboxamide 4 shows signals for two amide groups and one methylene group, as well as singlets for protons H-4 and NH. The HPLC/MS shows a peak [M+H] with m/z 213.6. Atom H-4 in the pyrimidine ring in the H-C HMBC spectrum gives four correlation peaks: δ-8.78/127.1 (H-4/C-5), 8.78/159.6 (H-4/C-2), 8.78/163.7 (H-4/5-CONH2), and 8.78/179.7 ppm (H-4/C-6). The CH2 group protons give two cross peaks: δ-3.69/159.6 (CH2/C-2) and 3.69/167.8 ppm (CH2/CO). The finding of cross peaks at δ 7.17/41.1

Transition Metal Salt-Mediated Radical Reactions of [60]Fullerene

Various transition metal salts have been employed to the radical reactions of [60]fullerene (C60). The present review article covers the reactions of C60 with active methylene compounds, methyl ketones, β-enamino carbonyl compounds, carboxylic acid derivatives, and diallylamines in the presence of Mn(OAc)3·2H2O affording the singly bonded fullerene dimers, 1,4-adducts and 1,16-adduct of C60, C60-fused dihydrofurans, methanofullerenes, C60-fused pyrrolines, C60-fused lactones, fullerenyl ester derivatives, and C60-fused pyrrolidines as well as the transformation of ArC60-H into ArC60-OAc by Mn(OAc)3·2H2O. Radical reactions of C60 promoted by other transition metal salts including copper(II), lead(IV), iron(III), ruthenium(II/III), tungsten(VI), cerium(IV) salts are also described. Keywords: [60]fullerene, Radical reactions, Transition metal salts, Manganese(III) acetate, Copper(II) acetate, Ferric perchlorate, Lead(IV) acetate, Tetrabutylammonium decatungstate, Ruthenium complex, Ferric nitrite, Ferric chloride, Ammonium cerium(IV) nitrate.

Unexpected manganese(iii) acetate-mediated reactions of β-enamino carbonyl compounds with 1-(pyridin-2-yl)-enones under mechanical milling conditions

The solvent-free reactions of β-enamino carbonyl compounds with 1-(pyridin-2-yl)-enones in the presence of manganese(iii) acetate dihydrate unexpectedly afforded 2-acyl-3-aryl-6,7-dihydro-4(5H)-benzofuran derivatives under mechanical milling conditions.

ChemInform Abstract: Synthesis of Pyridine Derivatives by the Three-Component Condensation of a β-Dicarbonyl Compound, β-Enaminocarbonyl Compound, and Ethyl Orthoformate.

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1,2-Acyl group migration in the oxidative free radical reaction of 2-substituted-1,4-quinones

Oxidative free radical reactions of 2-substituted-1,4-quinone derivatives are described. Electrophilic carbon-centered radical produced by the manganese(III) acetate oxidation of α-chloro-β-ketoester undergoes efficient addition to the C–C double bond of 5,6-dimethyl-2-(methylamino)-1,4-benzoquinone, and this reaction provides a novel method for the synthesis of spirolactam 3 and indole-2,4,7-trione 4. It shows high chemoselectivity depending on the migratory aptitude of the substituent on α-chloro-β-ketoester. Imine radical can be generated from the oxidation of β-enamino carbonyl compound with Mn(III) or Ce(IV) salt. With 2-hydroxy-1,4-naphthoquinone, spirolactam 6 was prepared from β-enamino carbonyl compound effectively. TBACN/CHCl 3 is the most effective reaction condition for the formation of 6.

Radical reactions of [60]fullerene with β-enamino carbonyl compounds mediated by manganese(iii) acetate

Manganese(III) acetate dihydrate-mediated reactions of [60]fullerene with beta-enamino carbonyl compounds afforded [60]fullerene-fused pyrroline derivatives, of which the nitrogen atom is directly connected to the fullerene cage. A possible reaction mechanism is proposed.

The Influence of the Ring Size of Thiolactams in the Eschenmoser Coupling Reaction in Presence of DBU. Formation of Bicyclic Thiazolidinones or Thioimines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The influence of the ring size of thiolactams in the Eschenmoser coupling reaction in presence of DBU. Formation of bicyclic thiazolidinones or thioimines

The different behaviors of pyrrolidin-2-thione and piperidin-2-thione under a modified Eschenmoser sulfur contraction reaction protocol using DBU as base was observed. The pyrrolidin-2-thione 1b follows the expected reaction course, leading to thioimines 5a–d, which can be transformed subsequently into the respective by action of a thiophile, while the piperidin-2-thione leads to the formation of bicyclic thiazolidinones 4b–d in moderate to good yields. The β-enaminocarbonyl compound 11 was hydrogenated to afford the respective five-membered analogue of methylphenidate 12.

A concise and stereoselective synthesis of (+/−)- erythro-methylphenidate

A concise and stereoselective synthesis of racemic erythro-methylphenidate ( 1 ) is described. The coupling reaction between piperidine-2-thione ( 3 ) and 2-bromo-2-phenylmethylacetate ( 4 ) afforded the β-enaminocarbonyl compound 2 in 60% yield by a modified Eschenmoser sulfide contraction reaction. In most cases the bicyclic thiazolidinone 5 was produced. Diastereoselective reduction of 2 in the presence of borohydrydes furnished the (+/−)- erythro-methylphenidate in good yields with dr >95%.

A novel oxidative free radical reaction between 2-hydroxy-1,4-naphthoquinone and β-enamino carbonyl compounds

The manganese(III) initiated oxidative free radical reaction between 2-hydroxy-1,4-naphthoquinone and β-enamino carbonyl compound 2 is described. Enamine radical 5 can be generated effectively from the oxidation of enamine 2 by manganese(III) acetate. Spirolactam 3 was prepared effectively from readily available 2-hydroxy-1,4-naphthoquinone and enamine 2 .